2(a) What are the differences between risks associated with exposure of persons to natural UVR and those risks from artificial UVR?

There are no physical differences in type of radiation between natural and artificial UVR per se. However, there are important differences in the spectral distribution and absolute and relative irradiances of UVR from the sun and artificial sources, and between different artificial sources as shown in Figure 1. There is no standard solar spectrum because this varies with factors such as season, latitude and time of day. From a physical standpoint, the UV emission from sun is primarily within the UVA range. Artificial emission spectra are different from solar emission spectra from a physical point of view.

It is relatively easy to compare the acute risks of exposure to natural and artificial UVR, which are similar, the details of which are discussed in Section 4. It is much more difficult to compare chronic effects which, in the sun, also depend on patterns of exposure.

Data on the risk of skin cancer associated with artificial UVR sources (see Section 4) are few compared with those related to sun exposure. Furthermore the tanning device studies are often uninformative because of small numbers of cases and controls, and low usage of the devices. There are also great difficulties in collecting adequate exposure data because of recall bias and lack of user knowledge of the type of UVR emitted by the devices. Many studies therefore have recorded only whether a tanning device has been used “ever” or “never” so that the power to address dose or age effects is limited.

Furthermore, tanning device users are often those who sunbathe frequently and it is likely that case-control studies are seriously confounded. There are some data published on the effects of medical use of artificial UVR sources. Although the UVR dose is considerably lower than that to which users of tanning devices are potentially exposed, such studies do have the merit of much more accurate dosage estimation.

Photo(chemo)therapy is used in the treatment of skin diseases. The use of psoralen plus UVA (PUVA) to treat psoriasis is known to cause skin cancer (Stern and Laird, 1994) but PUVA is mechanistically quite different from UVA and UVB and therefore is not relevant to the current discussion. In the PUVA cohort study reported by Stern from the United States, there was no discernable additional effect of exposure to UVB (Stern and Laird, 1994). In a study of psoriatics treated with coal tar and UVB in the 1950s followed up for 25 years there was no demonstrable increased risk of skin cancer but the numbers treated were relatively small (280) (Pittelkow et al, 1981). In an even smaller study of 195 German psoriatics treated with broadband (n=69) or narrow band UVB (n= 126) from 1994 to 2000 only one skin cancer had occurred by 2004. This was an in situ melanoma which developed in the same year that narrow band UVB therapy was begun (Weischer et al, 2004). A study in Scotland with a median follow up period of 4 years has shown a small increase in BCC after treatment with narrow band UVB phototherapy (Man et al, 2005).

Overall, the risks of skin cancer from the medicinal use of artificial UVR (in the absence of photosensitizers) appear to be small but the data are few and the dose to which the patients are exposed tends to be significantly smaller than users of commercial sunbeds are potentially exposed to. It is likely, from our knowledge of skin cancer and solar UVR, that the skin cancer risk attributable to artificial UVR will be greater in those who are genetically susceptible such as the fair skinned.

3.2 What are the health risks of UVA, UVB and UVC radiation?

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2(b) What are the differences regarding the health and safety risks with respect to exposure of persons to UVA, UVB and UVC radiation respectively?

Coblentz introduced the concept of the spectral regions UVA, UVB and UVC at the Second International Congress on Light in Copenhagen in 1932. These regions were determined by the transmission properties of three common glass filters; a barium-flint filter defined the UVA (315-400nm); a barium-flint-pyrex filter the UVB (280-315nm); and a pyrex filter defined the UVC (wavelengths shorter than 280nm). So the basis of these divisions has its grounding in physics, and not biology, although these definitions have been very useful in biology. Although these are the official designations of the Commission Internationale de l'Éclairage (CIE), other authorities, especially in the biological and clinical sciences, use different definitions such as UVA (320-400nm), UVB (290-320nm) and UVC (190-280nm). More recently, the terms UVA-I (340-400nm) and UVA-II (315-340nm) have come into use because of a better understanding of mechanistic differences between UVB and UVA. Mechanistically, UVA-II is similar to UVB in which the target molecule (e.g. DNA) is directly altered by its absorption of UVR energy. In contrast, UVA-I reactions tend to cause indirect damage to target molecules via reactive oxygen species (ROS) generated by UVR absorption by other molecules.

2(b).1 Acute Effects

The wavelength dependency of a given photobiological effect is demonstrated by its action spectrum, which depends on a variety of factors but is based on the absorption spectrum of the chromophore (UVR absorbing biomolecule) and the optical properties of the skin. Action spectroscopy and studies with different broad-spectrum sources show that UVB is much more effective than UVA for most acute endpoints studied in human skin. This includes erythema (Anders et al, 1995; CIE 1998; Young et al, 1998), delayed pigmentation (Parrish et al, 1982), DNA photodamage (Young et al, 1998) and UCA photoisomerization (McLoone et al, 2005). In general, UVB is 3 to 4 orders of magnitude more effective per unit physical dose (J/cm2) than UVA, but this difference depends on the specific wavelengths/wavebands being compared. Action spectra for immunosuppression in human skin are not available. UVB is known to be immunosuppressive but the role of UVA is still not clear (Phan et al, 2006). The action spectrum for IPD shows that UVA is more effective than UVB (Irwin et al, 1993).

UVC is not an issue for terrestrial solar UVR because it is completely absorbed by the ozone layer. In any case, UVC is strongly attenuated by chromophores in the upper epidermis (Young, 1997) and UVC-induced DNA damage in the dividing basal layer of human epidermis is not readily detected (Campbell et al, 1993; Chadwick et al, 1995) which may explain why the dose response curve for UVC erythema in human skin is very much less steep than for UVB (Diffey and Farr, 1991). It is unlikely that UVC from artificial sources presents an acute or long-term hazard to human skin. However, UVC is likely to cause acute photokeratitis.

Wavelength dependency is crucial in determining the biological effect of a given spectral region of a UVR source. For example, the 0.8% UVB content of a tanning lamp accounted for 75% of the CPD (cyclobutane pyrimidine dimers) that it induced in human keratinocytes in vitro (Woollons et al, 1999). Thus action spectra are essential as weighting functions to determine the biological effects of different broad-spectrum UVR emission spectra (see Section 5). Emission spectra without relevant action spectrum weighting are of very limited value in risk assessment. Action spectra are only valid if there is no interaction between different spectral regions. However, there is evidence that such interactions do occur at the cellular level (Schieke et al, 2005).

2(b).2 Chronic Effects

The wavelength dependencies for skin cancer (SCC) and photoageing (elastosis) have been determined in hairless mouse models (de Gruijl, 1995; Kligman and Sayre, 1991) and these studies have shown action spectra similar to that for human erythema (CIE, 1998; Young et al, 1998). Figure 2 shows the action spectra for human erythema and non-melanoma skin cancer (SCC) (CIE 1998, 2000) and it can be seen that these are very similar, especially in the solar UVB and UVA-II (315-340nm) ranges. Thus, one might conclude that erythema, primarily caused by UVB, can be regarded as a surrogate risk factor for SCC and photoageing. There is no animal model for UVR-induced BCC.

Sunburn, an important risk factor for melanoma, has therefore implicated UVB in its pathogenesis (Wang et al, 2001). The incidence of melanoma, as well as BCC and SCC, is very high in xeroderma pigmentosum (XP) with defective excision repair of UVB-type DNA damage, e.g CPD. The wavelength dependency for melanoma however is not yet established because of the lack of a good animal model (Noonan et al, 2003). Melanomas have proved extremely difficult to induce by UVR alone in mice. Wavelength dependency has been determined in a fish model (Xiphophorus) (Schartl et al, 1997) the value of which is limited because its melanoma- like lesions arise from the dermis instead of the epidermis and fish are phylogenetically very different from humans. Studies in these fish however showed that visible and UVA radiation, as well as UVB (Setlow et al, 1993) induced lesions that raised concern that UVA might be causal for human melanoma as well or instead of UVB. A mammalian opossum model also developed melanoma-like lesions after broad-band UVA exposure but with low potency compared to broad-band UVB (Robinson et al, 2000). A mouse model was described in 2003 (the hepatocyte growth factors/scatter factor transgenic mouse) in which melanomas with a strong epidermal component were induced (Nonnan et al, 2003). Neonatal UV irradiation was necessary and sufficient to induce melanoma although adult irradiation increased the number of lesions. In 2004 the same group reported studies using the mouse in which UVB but not UVA induced melanoma, providing perhaps more persuasive evidence that UVB exposure is causal rather than UVA (De Fabo et al, 2004).

Studies of somatic mutations in a variety of genes have been reported in the search for evidence to support a role for UVBexposure. Genes such as p53 have, however, failed to show the characteristic UVB signature C to T transitions and CC to TT mutations, providing additional concern that UVB may not be the only causal waveband. Recently, mutations in BRAF (downstream of RAS) were found in a majority of naevi and melanoma. The dominant point mutation (T1796A) is not characteristic of UVB radiation, but this does not exclude a causal role for UVR (de Gruijl, 2003).

It is more difficult to determine UVA induced mutagenesis because DNA does not significantly absorb UVA at doses obtained with solar exposure. It is thought that UVA induced mutagenesis is mainly mediated by photosensitising reactions that generate reactive oxygen species. In one system it was suggested that T to G transversions are typical of UVA induced damage (Drobetsky et al, 1995) but in another G to T transversions were seen as well as small tandem base deletions (Pfeifer et al, 2005). There is no consensus on UVA signature somatic mutations in tumours. Furthermore, it is possible that UVA may have an indirect adverse effect on the micro-environment in the dermis and dermo-epidermal junction by inducing growth factor release which may have a proliferative effect on melanocytes (Brenner et al, 2005).

In summary, UVB is likely to be the main cause of photoageing and SCC. Sunburn, a marker for excessive UVR exposure, is a risk factor for melanoma. UVB is the main cause of sunburn but this does not necessarily mean that it is the prime cause of melanoma, the spectral dependence of which remains unknown. The conservative approach is to restrict UVB and UVA exposure in susceptible phenotypes until wavelength dependency is established. UVC exposure is unlikely to cause acute or long-term damage to the skin but can cause severe acute damage to the eye and should not be permitted at all from any tanning device.